In Microsoft Excel 2013:
I have a spreadsheet (exported monthly from another program). My goal is to take the last row of data and subtract it from the first row of data
You can simplify the last number formula by using LOOKUP, i.e.
LOOKUP
=LOOKUP(9.99999999999999E+307,B:B)
and for the first number try this
=INDEX(B:B,MATCH(1,INDEX(ISNUMBER(B:B)+0,0),0))